Dataset Information

68Ga-NODAGA-Indole: An Allysine-Reactive Positron Emission Tomography Probe for Molecular Imaging of Pulmonary Fibrogenesis.

ABSTRACT: Oxidized collagen, wherein lysine residues are converted to the aldehyde allysine, is a universal feature of fibrogenesis, i.e. actively progressive fibrosis. Here we report the small molecule, allysine-binding positron emission tomography probe, 68Ga-NODAGA-indole, that can noninvasively detect and quantify pulmonary fibrogenesis. We demonstrate that the uptake of 68Ga-NODAGA-indole in actively fibrotic lungs is 7-fold higher than in control groups and that uptake is linearly correlated ( R2 = 0.98) with the concentration of lung allysine.

SUBMITTER: Wahsner J

PROVIDER: S-EPMC6494104 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

68Ga-NODAGA-Indole: An Allysine-Reactive Positron Emission Tomography Probe for Molecular Imaging of Pulmonary Fibrogenesis.

Wahsner Jessica J Désogère Pauline P Abston Eric E Graham-O'Regan Katherine A KA Wang Junfeng J Rotile Nicholas J NJ Schirmer Markus D MD Santos Ferreira Diêgo Dos DD Sui Jingyi J Fuchs Bryan C BC Lanuti Michael M Caravan Peter P

Journal of the American Chemical Society 20190327 14

Oxidized collagen, wherein lysine residues are converted to the aldehyde allysine, is a universal feature of fibrogenesis, i.e. actively progressive fibrosis. Here we report the small molecule, allysine-binding positron emission tomography probe, 68Ga-NODAGA-indole, that can noninvasively detect and quantify pulmonary fibrogenesis. We demonstrate that the uptake of 68Ga-NODAGA-indole in actively fibrotic lungs is 7-fold higher than in control groups and that uptake is linea ...[more]

PMID: 30908032

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

68Ga-NODAGA-Indole: An Allysine-Reactive Positron Emission Tomography Probe for Molecular Imaging of Pulmonary Fibrogenesis.

Publications

<sup>68</sup>Ga-NODAGA-Indole: An Allysine-Reactive Positron Emission Tomography Probe for Molecular Imaging of Pulmonary Fibrogenesis.

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